The general and long-term goal of my laboratory is to study autoantibody-mediated skin diseases in order to further our understanding not only of the pathophysiology of these diseases but also of the structure and function of normal epidermis and epidermal basement membrane zone (BMZ). Specifically, antibodies in these diseases define molecules in the normal epidermis. We have characterized the antigens defined by three of these diseases: bullous pemphigoid (BP), pemphigus vulgaris (PV), and pemphigus foliaceus (PF). We have defined the cells which synthesize these antigens, as well as the antigen defined by the autoantibodies found in patients with epidermolysis bullosa acquisita (EBA). We have demonstrated that BP antigen is distinct from other known BMZ molecules such as laminin and type IV collagen. Using these three molecules we have studied the BMZ of basal cell carcinoma and other epidermal tumors. We have also used three molecules to map, at a molecular level, the split in the BMZ in various hereditary mechanobullous diseases (epidermolysis bullosa). We have used the binding of antibodies to specific molecules to make diagnoses of EBA or BP in various complicated cases of these diseases. We have demonstrated that PV and PF autoantibodies bind distinct molecules. All PV autoantibodies bind the same molecule. We have used this fact to diagnosis certain patients with PV. Almost half of PF autoantibodies bind to a 155 kd glycoprotein which we have shown to be identical to desmoglein I, a desmosomal core glycoprotein.